About seven thousand rare (orphan) diseases are known in the world. Most of them are hereditary. Sometimes it takes years to find the genetic mutation that causes them, and the development of drugs is very expensive. RIA Novosti talks about projects for mass decoding of genomes and testing drugs for rare diseases.
“In Russia, according to the law, diseases that occur in ten out of a hundred thousand people are considered rare. How many such patients in the country are unknown. Nobody in the world is able to calculate this. According to some estimates, up to ten percent of the human population may suffer from orphan diseases,”says Ekaterina Zakharova, head of the laboratory at the Medical Genetic Research Center in Moscow.
People come to this center from all over the country; many complex genetic studies are carried out there for free. “Diagnostics of such diseases as the lottery. Someone is lucky, and doctors determine the cause quickly, in just a couple of months. And sometimes it takes years to find out the correct diagnosis. Before getting to us, patients go through endless examinations and analyzes, because specialists do not understand what is wrong with them,”the doctor continues.
A diagnostic odyssey
Anatoly Kryukov from Kolomna near Moscow is just one of those unlucky patients. Of the 34 years, 25 was spent on the diagnosis. The first alarming symptoms appeared at the age of seven. The fact that he had a deficiency of lysosomal acid lipase, Anatoly learned only in 2016, after a complete genetic analysis. This disease is caused by mutations in the LIPA gene, as a result of which lipase synthesis in the body is disrupted. The liver is severely affected in patients.
“They made different diagnoses: jaundice, hepatitis B, glycogenosis. Childhood and part of adult life were spent in hospitals. Ordinary hospital, then MONIKI, Scientific Center of Children's Health on Lomonosovsky Prospekt, clinic of the Scientific Research Institute of Nutrition. You stay for a month and a half, two weeks at home, and then again in the hospital,”says Kryukov.
And so all over the world. It is extremely difficult to determine an orphan disease for a doctor who may have never encountered it in his life.
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“The doctor diagnoses by symptoms and, first of all, checks typical diagnoses. For example, if a patient has abdominal pain, then most likely it is appendicitis, and not something rare - say, Fabry disease or porphyria,”Zakharova explains.
One hundred thousand broken genomes
To solve the problem systemically, in 2012 the UK launched an ambitious 100,000 Genome Project, supported by the public health service. The goal is to decipher the genomes of one hundred thousand people suffering from orphan diseases and rare forms of cancer.
Scientists intend to analyze the DNA of each patient and combine the obtained genetic data with personal medical records. This will help you better understand the disease and its complex relationships with genes, and predict how the patient's body will respond to a particular treatment.
The project is based on the concept of personalized medicine, which implies an individual approach to the patient, when genetic analysis is a key component in choosing or adjusting treatment. The problem is that there are no cures for most orphan diseases; they have yet to be developed. And this is possible only if the DNA sequence of a particular patient is known.
Human diseases are simulated on mice
Scientists from the Institute of Gene Biology of the Russian Academy of Sciences are participating in one of these projects to find individual drug therapy for the treatment of a rare form of Duchenne muscular dystrophy. Under the guidance of biologist Alexei Deikin, they artificially induce this disease in mice using a targeted gene mutation. And they test orphan drugs on rodents, before moving on to treating people, more precisely, one particular patient.
“This is a boy with a rare form of Duchenne dystrophy. Usually this disease is associated with a mutation in exon 52, but it has a different mutation. Therefore, the medicine used in the treatment of this disease is not suitable for him. Using the CRISPR / Cas9 gene editor, we created a mouse model that reproduces its genetic picture. We are now testing a gene therapy drug in rodents. If it proves its effectiveness, then clinical trials will follow and, we hope, successful treatment of the patient,”says Alexey Deikin.
In general, medicines for rare diseases are a big headache for pharmaceutical companies, doctors and patients. According to Irina Myasnikova, chairman of the board of the All-Russian Society of Orphan Diseases, only about seventy out of seven thousand such ailments have at least some kind of therapy, and there are very few registered orphan drugs.
The first issue is cost. Medicines for rare diseases are usually expensive, because development costs the same as drugs for mass diseases, and it is simply not profitable for pharmaceutical companies to invest.
The second problem is clinical trials, in which at least three thousand people must participate. If the disease is rare, so many patients simply cannot be found.
“The development of orphan drugs cannot be done without state support, and it must be constantly expanded. Even now, there are only about a thousand rare diseases on the list of the Ministry of Health, and several dozen new ones are discovered every year. And patients should be able to receive adequate and timely treatment,”concludes Myasnikova.
Alfiya Enikeeva